Abstract
Tolerance to self-antigens expressed in peripheral organs is maintained by CD4(+) CD25(+) Foxp3(+) Treg cells, which are generated as a result of thymic selection or peripheral induction. Here, we demonstrate that steady-state migratory DCs from the skin mediated Treg conversion in draining lymph nodes of mice. These DCs displayed a partially mature MHC II(int) CD86(int) CD40(hi) CCR7(+) phenotype, used endogenous TGF-β for conversion and showed nuclear RelB translocation. Deficiency of the alternative NF-κB signaling pathway (RelB/p52) reduced steady-state migration of DCs. These DCs transported and directly presented soluble OVA provided by s.c. implanted osmotic minipumps, as well as cell-associated epidermal OVA in transgenic K5-mOVA mice to CD4(+) OVA-specific TCR-transgenic OT-II T cells. The langerin(+) dermal DC subset, but not epidermal Langerhans cells, mediated conversion of naive OT-II×RAG-1(-/-) T cells into proliferating CD4(+) CD25(+) Foxp3(+) Tregs. Thus, our data suggest that steady-state migratory RelB(+) TGF-β(+) langerin(+) dermal DCs mediate peripheral Treg conversion in response to epidermal antigen in skin-draining lymph nodes.
Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigens, CD / analysis
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Antigens, Surface / analysis
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CD4 Antigens / analysis
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Cell Differentiation
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Cell Movement
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Fluorescent Antibody Technique
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Forkhead Transcription Factors / genetics
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Forkhead Transcription Factors / metabolism
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Immunophenotyping
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Integrin alpha Chains / analysis
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Interleukin-2 Receptor alpha Subunit / analysis
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Langerhans Cells / immunology*
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Langerhans Cells / metabolism
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Lectins, C-Type / analysis
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Lymph Nodes / immunology*
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Lymph Nodes / metabolism
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Major Histocompatibility Complex
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Mannose-Binding Lectins / analysis
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Mice
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Mice, Inbred C57BL
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Mice, Transgenic
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Microscopy, Confocal
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NF-kappa B / deficiency
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NF-kappa B / immunology
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Receptors, CCR7 / analysis
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Self Tolerance
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Skin / immunology*
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T-Lymphocytes, Regulatory / immunology*
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T-Lymphocytes, Regulatory / metabolism
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Transcription Factor RelB / analysis
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Transforming Growth Factor beta / metabolism
Substances
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Antigens, CD
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Antigens, Surface
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CD4 Antigens
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Ccr7 protein, mouse
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Cd207 protein, mouse
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Forkhead Transcription Factors
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Foxp3 protein, mouse
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Integrin alpha Chains
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Interleukin-2 Receptor alpha Subunit
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Lectins, C-Type
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Mannose-Binding Lectins
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NF-kappa B
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Receptors, CCR7
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Relb protein, mouse
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Transforming Growth Factor beta
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alpha E integrins
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Transcription Factor RelB